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Idarucizumab immediately reversed the anticoagulant effect of dabigatran in 100 percent of patients1

Updated results of 494 patients from largest study investigating a reversal agent for a novel oral anticoagulant in real-world emergency settings1,2

Data presented at AHA Scientific Sessions 20161

Ingelheim, Germany, 16 November 2016 – Boehringer Ingelheim announced updated results from data for 494 patients participating in the ongoing phase III RE-VERSE AD™ study, which showed that administration of 5g of idarucizumab immediately reversed the anticoagulant effect of dabigatran, the active ingredient in Pradaxa® (dabigatran etexilate).1 Idarucizumab, marketed as Praxbind®, is the first and only approved specific reversal agent for a non vitamin K antagonist oral anticoagulant (NOAC) and RE-VERSE AD™ is the largest patient study investigating a reversal agent for a NOAC.2-4 The updated results were presented at the American Heart Association (AHA) Scientific Sessions 2016 in New Orleans, Louisiana.1

RE-VERSE AD™ includes the types of patients healthcare professionals may treat in real-world emergency settings.2 The study enrolled patients treated with dabigatran who had uncontrolled or life-threatening bleeding (Group A, n=298, 60 percent) or required emergency surgery or an invasive procedure (Group B, n=196, 40 percent).1 This includes severely ill or injured patients (e.g. patients in an automobile accident with multiple injuries, patients with aortic aneurysm or patients receiving an organ transplant) who as such require urgent reversal of dabigatran.2

The primary endpoint of reversal of the anticoagulant effect of dabigatran within four hours was 100 percent1,2, as measured by diluted thrombin time (dTT) and ecarin clotting time (ECT) (95% CI, 100-100).1,2 Of note, reversal was evident immediately after administration of idarucizumab.1 For Group A patients with extracranial bleeding, median time to confirmation of haemostasis was 3.5 to 4.5 hours, depending on anatomical location.1 The source of bleeding was similar to the previous interim analysis (45 percent gastrointestinal, 33 percent intracranial haemorrhage).1,5 In Group B, 93 percent of patients experienced normal haemostasis during surgery, and the median time to the operating room was 1.6 hours after administration of idarucizumab.1

No safety signals attributed to idarucizumab were detected. All serious adverse events reported were considered to be related to the index event or comorbidities rather than to study treatment. Thrombotic events occurred in 6.3 percent (31/494) of patients within 90 days after idarucizumab administration. Approximately two-thirds of these patients received no anticoagulation prior to the event. Mortality rates were 12.3 percent (Group A) and 12.4 percent (Group B) at 30 days, and 18.7 percent (Group A) and 18.5 percent (Group B) at 90 days.1

“The availability of idarucizumab as a reversal agent for dabigatran is an important development in anticoagulation care, and RE-VERSE AD™ is the most robust examination of its real-world use and impact,” said Dr. Charles Pollack, lead investigator of RE-VERSE AD™, Professor of Emergency Medicine, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, US. “These results further support that, although idarucizumab is likely to be rarely used in light of the safety profile of dabigatran, a specific reversal agent provides an important therapeutic option for physicians and patients.”

“With these results, we have an unprecedented wealth of data on the use and effects of idarucizumab in urgent situations,” said Professor Jörg Kreuzer, Vice President Medicine, Therapeutic Area Cardiovascular, Boehringer Ingelheim. “These insights, together with the confirmed safety profile of dabigatran, can truly give physicians confidence in choosing a NOAC that provides a new level of care for their patients.”

NOTES TO THE EDITORS

About the RE-VERSE AD™ study
RE-VERSE AD™ is an ongoing phase III global study that includes patients taking dabigatran who require urgent procedures or have uncontrolled bleeding.2 The interim analysis from RE-VERSE AD™ included data from patients requiring urgent procedures / emergency surgery, e.g. surgery for an open fracture after a fall, or patients with either uncontrolled or life-threatening bleeding complications, e.g. intracranial hemorrhage or severe trauma after a car accident.2,5 The primary endpoint, the degree of reversal of the anticoagulant effect of dabigatran achieved by idarucizumab within four hours, was measured by diluted thrombin time (dTT) and ecarin clotting time (ECT).2

The study is the first of its kind in patients, and has been underway since May 2014, enrolling up to 500 patients in more than 35 countries.5,6

About idarucizumab (Praxbind®)
Idarucizumab is a humanized antibody fragment, or Fab, designed as a specific reversal agent to dabigatran.7 Idarucizumab binds specifically to dabigatran molecules only, neutralising their anticoagulant effect without interfering with the coagulation cascade.2,7

In the EU and US, idarucizumab is now indicated for patients treated with dabigatran when reversal of the anticoagulant effects of dabigatran is needed:3,4

For urgent procedures / emergency surgery

In life-threatening or uncontrolled bleeding

Regulatory reviews and submissions in other countries are ongoing. Boehringer Ingelheim plans to submit idarucizumab in all countries where dabigatran is licensed.8

About dabigatran etexilate (Pradaxa®)
Clinical experience of dabigatran equates to over 5 million patient-years in all licensed indications worldwide. Dabigatran has been in the market for more than 7 years and is approved in over 100 countries.8

Currently approved indications for dabigatran are:9,10

Prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation and a risk factor for stroke

Treatment of DVT and PE and the prevention of recurrent DVT and recurrent PE in adults

Dabigatran, a direct thrombin inhibitor (DTI), was the first widely approved drug in a new generation of direct oral anticoagulants, available to target a high unmet medical need in the prevention and treatment of acute and chronic thromboembolic diseases.9-11 Potent antithrombotic effects are achieved with direct thrombin inhibitors by specifically blocking the activity of thrombin, the central enzyme in the process responsible for clot (thrombus) formation.12 In contrast to vitamin K antagonists, which variably act via different coagulation factors, dabigatran provides effective, predictable and reproducible anticoagulation with a low potential for drug-drug interactions and no drug-food interactions, without the need for routine coagulation monitoring or mandatory dose adjustment.11,13

Dabigatran is the only novel oral anticoagulant with an approved reversal agent. Praxbind® (idarucizumab) is approved in the European Union and United States for adult patients treated with Pradaxa® who require rapid reversal of its anticoagulant effects prior to urgent procedures/emergency surgery or in life threatening or uncontrolled bleeding.3,4

About Boehringer Ingelheim
Boehringer Ingelheim is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, Boehringer Ingelheim operates globally through 145 affiliates and a total of some 47,500 employees. The focus of the family-owned company, founded in 1885, is on researching, developing, manufacturing and marketing new medications of high therapeutic value for human and veterinary medicine.

Social responsibility is an important element of the corporate culture at Boehringer Ingelheim. This includes worldwide involvement in social projects through, for example, the initiative “Making More Health” while also caring for employees. Respect, equal opportunity and reconciling career and family form the foundation of mutual cooperation. The company also focuses on environmental protection and sustainability in everything it does.

This press release is issued from our Corporate Headquarters in Ingelheim, Germany and is intended to provide information about our global business. Please be aware that information relating to the approval status and labels of approved products may vary from country to country, and a country-specific press release on this topic may have been issued in the countries where we do business.